I recently begin using Bricklink to acquire pieces for some custom modular building. I am primarily doing this to make a larger more diverse lego city to display. These custom modular buildings are not cheap when compared to the official modular buildings. Outside of setting up my own Bricklink shop and selling off the pieces, do you think there will be any chance of profit/break even by ebaying off the entire building in the future?

Many people do sell their own complete custom kits, and usually list them for A LOT. I've never listed a kit or even just a set of instructions for sale myself, so I'm not sure of exact profits. But I think if the design has a good enough "Wow" factor, you could make a nice profit if you plan to later on sell your custom modular, depending on how you obtained the parts used in the first place. You never know just how much someone is willing to pay for a good design til you try.

I will pay top dollar for an awesome custom set, even though I know that it is a losing proposition when talking about price per piece.

I think you should look at custom building by combining existing sets to cut down on cost. For example you can create a custom building just from using Tower Bridge and Pet Shop. Or using Fire Brigade and Town Hall. Either way you could create something quite unique and likely have enough pieces left over to combine with some other set. There are people on who sell custom builds, but I have no idea if they are going up in value. Custom builds will be worth more if you can create something more unique than simply another walkup apartment building. Create something that Lego hasn't done yet but would fit in with the other modulars - hospital, gymnasium, school, museum, chinese restaurant, etc.

What Talon just said is a good idea that has great potential....Alternates.

You just buy one modular or perhaps a couple of smaller sets and you have ALL the parts at your disposal.

It's a nice setup that needs to be exploited a little more.

Speaking of which, Brick City Depot has just created another alternate design. This time for the "Haunted House"!

It looks like the original house before it became dilapidated and old. Check it out!

Your best bet if you are going the Custom Modular route is to do actual brands, 'Chilis, Starbucks, etc'. People who do custom toys outside of Legos make quite amount of money doing unreleased licensed goods.

Yes, modulars based on real world franchises add a nice touch of realism. I also like ones based on real architectural design styles, like San Francisco or Chicago style. Parts of Europe has some nice looks to them as well.